Bioencapsulation, which has provided a range of promising therapeutic treatments for diabetes, hemophilia, cancer, and renal failure, emerged as a new area for research for biomedical engineering in 1964 with the use of ultrathin polymer membrane microcapsules, or “artificial cells”, for the immunoprotection of transplanted cells. [Chang, Science 146, 524-525 (1964)]. Twenty years later, bioencapsulation was successfully implemented to mobilize xenograft islet cells. When implanted in a rat [Lim et al., Science 210, 908-909 (1980)], the microencapsulated islet corrected the diabetic state for several weeks. Since then, there has been significant progress towards understanding the biological and technological requirements for successful transplantation of encapsulated cells in vivo.
Cell encapsulation has traditionally been accomplished by extruding the droplets carrying the cells through a nozzle (air/water emulsion) into a bath containing the polymerizing agent. These methods have their disadvantages including, e.g., a minimum droplet size, an increase in size dispersion for small droplet sizes, an inability to trap the droplets before (or without) polymerization, and non-uniform polymerization times across droplet population.
FIG. 1 provides an illustration of current encapsulation methods in which capsules are formulated by droplet extrusion or emulsification. In the extrusion techniques, often referred to as the drop method, solutions are extruded through a small tube or needle, permitting the formed droplets to freely fall into a gelation bath. The droplets are cross-linked by addition of appropriate reagent to the receiving solution. A typical example is the formation of alginate beads by dropping a sodium alginate solution into a bath containing calcium chloride. In the emulsion technique, solutions are mixed and dispersed in a non-miscible phase often facilitated with a surfactant. When the dispersion reaches the equilibrium, gelating and/or membrane formation is initiated by cooling and/or addition of gelling agent to the emulsion, or by introduction of a cross-linked agent. These methods produce larger droplets. Also, droplets formed by the extrusion method have different membrane thickness and size as they drop in the gelation bath at different time.
Thus, it would be desirable to provide improved apparatus and methods for the encapsulation of cells with low and high cell densities.